The electrophysiological studies proposed here seek to contribute to the discovery of the neuronal functions of K+ channels of the Eag family. Members of the Eag family have intriguing structural and electrophysiological properties, suggesting a unique role in neuronal excitability. Little is known, however, about their distribution and functions in neurons. This project is focused on Eag2, one of the members of this family. Eag2 channels have unique electrophysiological properties and a highly specific pattern of expression in layer IV of the rat neocortex. Layer IV cortical neurons are the main recipient of the thalamocortical (TC) input, bringing into the neocortex most sensory information. The goal of these experiments is to identify and characterize the currents carried by native channels containing Eag subunits in neurons, and to uncover their role in excitability. These experiments will test the hypothesis that Eag channels play special roles in the excitability of layer IV cortical neurons and in particular in mediating responses to modulators of cortical function such as ACh. ACh acting through muscarinic receptors is important in modulating cortical activity, playing major roles in attention-arousal and learning and memory. This proposal promises to provide new insights into the regulatory mechanism of behavioral state-dependent entry of sensory information to the cerebral cortex, as well as different mental disease states involving related modulatory pathways.